Valganciclovir is a mono-valyl ester pro-drug of ganciclovir, which is rapidly converted to ganciclovir on absorption. Valganciclovir is approved for the treatment of Cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS), and for the prevention of CMV disease in kidney, heart, and kidney-pancreas high-risk transplant patients. The formulation used in this study will be valganciclovir oral solution which is commercially available. It will be provided as a 12g powder containing 5g valganciclovir free base. The oral solution formulation comprises the following excipients: Providone K30, fumaric acid, sodium benzoate, sodium saccharin, mannitol, flavor, and purified water. The valganciclovir oral solution formulation does not contain lactose anhydrous.

The placebo comparator will be commercially available Simple Syrup (Syrup NF) as 60-90% sucrose in purified water.

Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:

The proportion of children whose change in total ear hearing assessments (improved + no change versus other) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The proportion of children who have change in best ear hearing assessments [improved + no change (normal to normal) versus other; and worse versus other] [ Time Frame: Baseline to Study Month 6 ] [ Designated as safety issue: No ]

The quantitative log reduction in viruria [ Time Frame: Baseline to end of 6 weeks of therapy ] [ Designated as safety issue: No ]

The proportion of children who have viremia [ Time Frame: 6 weeks and six months after trial entry ] [ Designated as safety issue: No ]

The quantitative log reduction in viremia [ Time Frame: Baseline to end of 6 weeks of therapy ] [ Designated as safety issue: No ]

The proportion of children who have CMV detected in saliva by PCR [ Time Frame: 6 weeks and six months after trial entry ] [ Designated as safety issue: No ]

The quantitative log reduction in CMV viral load in saliva [ Time Frame: Baseline to end of 6 weeks of therapy ] [ Designated as safety issue: No ]

The proportion of children whose sensorineural hearing improves or remains unchanged from baseline when measured [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]

The correlation of change in viral load with change in total ear and best ear hearing [ Time Frame: Baseline to 6 weeks of therapy ] [ Designated as safety issue: No ]

Valganciclovir will be administered at 16mg/kg body weight twice daily

Placebo Comparator: Placebo

Drug: Placebo

The placebo comparator will be commercially available Simple Syrup as 60-90% sucrose.

Detailed Description:

Upon enrollment, defined as informed consent signed and confirmed eligibility, study subjects will be randomized, when diagnosis of congenital CMV is confirmed, to six weeks of oral valganciclovir or six weeks of oral placebo. Study subjects will be stratified according to age at randomization (1 through 11 months, 12 through 23 months, 24 through35 months, and greater than or equal to 36 months)and according to country of enrollment (U.S. or U.K.). The sample size of randomized evaluable subjects is 54. Dropouts and subjects with audiology assessments that are inadequate for study comparison will be replaced (up to 20%, or n=10). During the six week treatment period, study subjects will be followed every 2 weeks. Subjects will also be seen at approximately one month following the final dose (Study Day 70), and again at Study Months 4 and 6.

At each of the visits during the treatment phase (Study Days 1, 14, 28, and 42), safety labs will be assessed; viral load specimens from blood, urine, and saliva will be obtained; adverse events will be assessed; and concurrent medications will be recorded. Ganciclovir concentrations for population pharmacokinetic assessment will be obtained at each study visit while the subject is receiving study medication. Dose adjustments for weight change will occur at study visits during the subject's treatment period, and may also occur at any time during the treatment period as indicated per protocol for neutropenia, thrombocytopenia, or renal impairment. At the Study Day 70 visit, safety labs will be obtained; viral load specimens from blood, urine, and saliva will be obtained; and adverse events will be assessed. Hearing will be assessed at baseline and at Study Month 6.

Changes in whole blood viral load measurements will be correlated with hearing outcomes. In study subjects with increasing whole blood viral loads during the course of treatment, antiviral resistance may be evaluated. A Data and Safety Monitoring Board (DSMB) will be established to oversee the accrual, performance, safety, and efficacy of the trial.

Eligibility

Ages Eligible for Study:

1 Month to 48 Months (Child)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Signed informed consent from parent(s) or legal guardian(s)

Sensorineural hearing loss (≥ 21dB in one or both ears, documented within 12 weeks prior to study entry)

Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)

Documented renal insufficiency, as noted by a creatinine clearance < 10 mL/min/1.73m2 at time of study enrollment

Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribavir

Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry).

Current receipt of other investigational drugs

Previous receipt of ganciclovir or valganciclovir

Known hypersensitivity to ganciclovir, valganciclovir, or components of the product

Inability to attend follow-up hearing and clinical assessments

Infants with Auditory neuropathy/dyssynchrony.

Children with another known etiology for SNHL (e.g. connexin 26, syndrome or metabolic disorder associated with SNHL, inner ear malformation and widened vestibular aqueducts, meningitis). Exclusion of each of these conditions is not required for trial enrollment.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01649869